The discovery of the gastric pathogen Helicobacter pylori nearly 30 years ago has drastically altered the treatment of peptic ulcer disease. By means of a horizontally acquired pathogenicity island, the cag PAI, H. pylori translocates an effector protein into host gastric mucosal cells mediating severe inflammation and carcinogenesis. Although the cag PAI is a critical determinant of virulence, not all persons infected with H. pylor develop severe disease. This is in part due to the existence of H. pylori strains that do not possess this pathogenicity island. Our lab has found genetic loci present in these cag PAI negative isolates that are frequently absent or highly mutated in the more virulent, cag PAI positive H. pylori isolates. The specific aims of this project are to characterize a gene found frequently among the H. pylori strains of lesser virulence, but infrequently among those associated with more severe disease. We hypothesize this gene, p7, is variably expressed in those cag PAI negative strains that possess it. We also aim to examine more cag PAI negative isolates for a bacteriophage found frequently as a prophage in these strains, but found very rarely among the more virulent, cag PAI positive isolates. Lastly, we propose to determine the complete genome sequence of four cag PAI negative H. pylori isolates from patients with no known disease associated with H. pylori. This effort will take advantage of next generation sequencing technology and be accomplished as part of a freshman biology laboratory class. PUBLIC HEALTH RELEVANCE: While some people infected with the stomach pathogenic bacterium, Helicobacter pylori develop gastric or duodenal ulcers or even gastric cancer, most of those infected with this pathogen remain asymptomatic for their lives. While many strains of this bacterium have a section of the genome dedicated to secreting a bacterial protein into stomach cells to induce inflammation and cancer, some strains of this bacterium do not. To examine the evolution of virulence in this significant human pathogen, more research is needed on the genomes of H. pylori strains that produce disease less frequently